Approximately five thousand infants under the age of one die in the United States each year for unexplained reasons, their death ultimately being classified as being caused by "Sudden Infant Death Syndrome" ("SIDS"). The cause of SIDS is not known and no methods for identifying those babies that either have SIDS or are at high risk of developing SIDS, have been previously disclosed.
Prior investigators have suggested that Sudden Infant Death may be related to elevated immunoglobulin concentrations. Urquhart et al., Sudden Unexplained Death in Infancy and Hyperimmunization, J. Clin. Path.; 24:736-739 (Feb. 24, 1971). Urquhart et al. determined postmortem antibody levels in SIDS cases. Urquhart et al.'s studies showed that antiglobulin antibodies were detected in Sudden Infant Death cases more frequently (56%) than in living control cases (5%). Urquhart et al. suggest that anti-antibodies might participate in fatal anaphylaxis in SIDS cases. However, Urquhart et al. did not suggest any technique for identifying newborns who are at elevated risk for SIDS, where the identification can be made at a time early enough to implement measures to prevent premature death.
Various assays have been utilized for quantitating IgM levels. For example, ELISA assays for IgM have been used to diagnose infectious diseases. IgM is a desirable indicator for this purpose because it is generally detectable in the early stages of an infection. These methods employ direct and indirect techniques to quantitate the amount of IgM which is specific for a particular infectious disease related antigen. An objective, when performing IgM assays to detect a specific disease, is to avoid interference from MAG. Wilson et al., Enzyme-Based Methods for IgM Serology: Standard Indirect ELISA vs Antibody-Capture ELISA, Laboratory Medicine, Vol. 23, No. 4, Pages 259-263 (April 1992). Thus, ELISAs designed to detect specific infectious diseases do not measure MAG levels, but instead seek to measure antigen specific IgM and to avoid signal generation or interference caused by fluctuating MAG levels.
Assays for a particular type of anti-IgG antibody, namely, relatively high affinity anti-IgG in adults, "rheumatoid factor" ("RF"), are used clinically to diagnose or monitor rheumatoid arthritis. Some tests for RF fail to discriminate between MAG and other anti-IgG antibodies such as IgG-anti-IgG and IgA-anti-IgG. Other RF tests specifically detect MAG. For example, a typical test for RF involves preparation of a solid phase with adsorbed human IgG. See Ziola et al., Determination of Human Immunoglobulin M Rheumatoid Factor by a Solid-Phase Radioimmunoassay Which Uses Human Immunoglobulin G in Antigen-Antibody Complexes, Journal of Clinical Microbiology, Vol. 8, No. 2, Pages 134-141 (August 1978). However, no one has suggested use of an RF test to detect elevated anti-IgG antibody levels in newborns for the purpose of identifying babies who are at high risk for SIDS. Further, current RF assays are designed to detect relatively high affinity MAG in adults. The RF tests are believed to be inadequate for detecting relatively lower affinity MAG which is typically present in newborns in association with IgG and antigen apparently related to perinatal disease infection.